The studies have continuud to examine the role of diabetes and arterial lipid metablism in atherogenesis. During the past year, most significant findings include: 1. Arterial fatty acyl CoA synthetase activity has been studied in control and cholesterol-fed rabbits to determine whether any increase in its activity was involved in the augmented cholesteryl ester synthesis observed with atherogenesis. No change in activity of the enzyme occurred with cholesterol feeding despite marked increases in fatty acyl CoA:cholesterol cyl transferase activity. Inhibition of both enzymes occurred with clofibrate and its tetrahydronapthyl analog (TPIA) added in vitro. 2. Fatty acyl CoA and cholesterol ester formation were examined in microsomal fractions from liver and adrenal gland. Fatty acyl CoA was the required precursor for the incorporation of oleic acid into phospholipid and cholesteryl ester. Clofibrate and TPIA inhibited the formation of both fatty acyl CoA and cholesteryl ester from oleic acid. 3. A new assay system for measuring cholesteryl ester hydrolysis has been developed utilizing cholesteryl ester that has been incorporated into liposomes. In rat liver, two different cholesteryl ester hydrolases were apparent, one which appeared to be lysosomal in nature and the second in the 150,000g supernatant fraction with pH optimum of about 8.5. In aortic tissue, only acid hydrolase activity was demonstrable. Cholesterol feeding in rabbits produced a slight decrease in the acid hydrolase activity despite marked increases in activity of several arterial lysosomal enzymes studied. Bibliographic references: Brecher, P.I., Kessler, M., and Chobanian, A.V.: Inhibition of fatty acid and cholesterol esterification in rat liver and adrenal microsomes by hypolipidemic agents. Fed. Proc. 34:633, 1975; Brecher, P.I., Chobanian, J., Small, D., and Chobanian, A.V.: Cholesteryl ester hydrolysis in liver and aorta using liposomes as substrate for in vitro studies. Circulation, October, 1975.